Analysis of 16 different matrix metalloproteinases (MMP-1 to MMP-20) in the synovial membrane: different profiles in trauma and rheumatoid arthritis

Objective-To define the pattern of mRNA expression of all human matrix meta lloproteinases (MMPs) described to date in rheumatoid arthritis (RA) and tr aumatic synovial membrane, in order to differentiate between a physiologica l tissue remodelling pattern and that associated with inflammatory tissue d estruction. Methods-Analysis of SwissProt protein and EMBL/GenBank nucleotide sequence banks, protein sequence alignment, reverse transcriptase-polymerase chain r eaction and nucleotide sequencing were used. Results-MMP-2 (gelatinase A), MMP-3 (stromelysin-1), MMP-11 (stromelysin-3) and MMP-19 were constitutively expressed. MMP-1 (fibroblast type collagena se), MMP-9 (gelatinase B) and MMP-14 (MT1-MMP) were expressed in all RA, bu t only in 55-80% of trauma samples. MMP-13 (collagenase-3) and MMP-15 (MT2- MMP) were expressed exclusively in RA (80-90% of the samples). MMP-20 (enam elysin) was absent and MMP-8 (collagenase-2) was rarely found in RA or trau ma. All other MMPs (-7, -10, -12, -16, -17) had an intermediate pattern of expression. Conclusions-Some MMPs without interstitial collagenase activity seem to hav e a constitutive pattern of expression and probably participate in physiolo gical synovial tissue remodelling. Some MMPs are exclusively associated to RA synovitis, for example, MMP-13, which preferentially degrades type II co llagen and aggrecan, and MMP-15, which activates proMMP-2 and proMMP-13 and is involved in tumour necrosis factor a processing. This clear cut rheumat oid/inflammatory MMP profile, more complex than has been previously appreci ated, may facilitate inflammatory tissue destruction in RA.